ABSTRACT ? CHEMICAL LIBRARY SCREENING SHARED RESOURCE The Chemical Library Screening (CLS) Shared Resource is managed by the Cancer Center. This resource offers Center scientists the ability to develop and conduct small- and large-scale chemical library screens and perform hit optimization and validation for generating selective probes/leads modulating biochemical and cellular processes in cancer. In addition, CLS provides faculty with access to technology, expertise, and infrastructure resources to develop novel assays for characterizing cellular targets involved in tumor initiation and pathogenesis and to advance the development of new lead molecules for anti-tumor therapies. CLS consists of four specialized but highly integrated facilities: High-Throughput Assay Development (HT-AD), Compound Management and High-Throughput Screening (CM-HTS), High-Content Screening (HCS), and Medicinal Chemistry and Drug Metabolism/Pharmacokinetics (MedChem/DMPK). The facilities physically reside within the Conrad Prebys Center for Chemical Genomics (Prebys Center) at SBP, which occupies more than 12,000 sq. ft. of laboratory space and houses substantial HTS and HCS assay development and screening instrumentation capabilities. CLS has access to a broad spectrum of diverse and focused small-molecule collections, several integrated liquid handling systems, and a plethora of detection instruments, capable of performing assays in any mode, including live-cell image-based assays requiring temperature and CO2 control. The Prebys Center grew out of the Cancer Center's CLS Shared Resource, which was initiated in the 2003 CCSG renewal. This support has been leveraged with several large grant awards and philanthropic funds. Initially awarded a grant as one of ten NIH Molecular Libraries Screening Network Comprehensive Centers, the Prebys Center was later selected as one of four NIH- designated Molecular Libraries Probe Production Centers Network comprehensive screening centers. It is also one of seven dedicated Centers for the NCI Chemical Biology Consortium (CBC). Despite the growth of the Prebys Center, the CLS Core remains of crucial importance to Center investigators because it provides an important interactive entry point to ensure that they derive the maximum scientific benefit from these world class chemical biology and drug discovery capabilities, enabling both fundamental and translational scientific endeavors. In the past 5 years, the Core has additionally enabled >100 assay development projects for Cancer Center investigators, resulting in >25 full HTS campaigns to support the goal of early translation. It has provided services for 36 Center investigators representing all three programs. The data generated have supported 24 successful grants from 16 Center members and numerous publications, including 20 publications co-authored by CLS staff.